Journal
JOURNAL OF CONTROLLED RELEASE
Volume 168, Issue 3, Pages 271-279Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2013.03.025
Keywords
Bioreducible nanogel; Vaccine adjuvant; Antigen presentation; Antibody production; Cytotoxic T-lymphocyte response
Funding
- National Natural Science Foundation of China [81171446]
- Guangdong Innovation Research Team Fund for Low-cost Healthcare Technologies (GIRTF-LCHT)
- Science and Technology Program of Guangdong Province [2012B090400043, 2012B090600036]
- Shenzhen Science and Technology Program [JC201005260247A]
- Chinese Academy of Sciences
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Although polysaccharide nanogels have emerged as a novel antigen delivery system for vaccine development, whether modulating the redox sensitivity of nanogels could improve vaccine efficacy remains unclear. In the present study, we generated bioreducible cationic alginate-polyethylenimine (PEI) nanogels as a novel vaccine delivery system. Briefly, nanogels were prepared by the electrostatic interaction of negatively charged alginate sodium with branched PEI2k, followed by disulfide cross-linking to generate bioreducible nanogels (AP-SS). The AP-SS nanogels demonstrated great antigen-loading capacity and minimal cytotoxicity. The in vitro study showed that reducible AP-SS nanogels not only facilitated antigen uptake by mouse bone marrow dendritic cells (BMDCs), but also promoted intracellular antigen degradation and cytosolic release. Moreover, AP-SS nanogels significantly enhanced both MHC class I and II antigen presentation by BMDCs. Compared with the non-reducible nanogels, AP-SS nanogels more potently enhanced vaccine-induced antibody production and CD8(+) T cell-mediated tumor cell lysis. Hence, the bioreducible alginate-PEI nanogels could serve as a potent adjuvant to improve vaccine-elicited humoral and cellular immune responses. (C) 2013 Elsevier B.V. All rights reserved.
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